The overall objective of this project is to carry out a systematic investigation of the factors which affect lead pharmacokinetics in experimental animals. Parameters which can potentially affect lead absorption, distribution and elimination are studied as potential avenues for lead poisoning prevention and treatment. We have examined the relationship between lead concentration in the mucosal bathing fluid of in vitro everted rat intestines and the flux of lead through those intestines. Segments of intestine (20 cm) approximately 13 cm from the pylorus were obtained from 200-300 g rats. Flux of lead through the intestines did not increase in proportion to bath lead concentration from 0.25 to 10.0 micrograms/ml. Uptake of lead by the intestinal tissue, measured at the end of the incubation, also exhibited similar concentration dependence. Flux at 1 microgram/ml (Pb) (2.73 plus or minus 0.41 ng/min; mean plus or minus SE, n equals 9) was slightly reduced by either anoxia (1.75 plus or minus 0.08; n equals 7, p less then 0.10) or 0.02 M NaF (1.20 plus or minus 0.20; n equals 7, p less then 0.02). The whole blood AUCO-4 days, obtained after oral administration of lead acetate solutions to rats in vivo was also dose-dependent. The relative AUCO-4 days after 1, 10, and 100 mg/kg oral doses were 1, 2.5, and 6.1, respectively. No dose-dependent total body lead clearance and renal clearance was observed between bolus intravenous doses of 0.5 mg/kg to 15.0 mg/k. A saturable mechanism for lead transport through rat intestine in vitro and in vivo is therefore indicated. The proposed work seeks to formulate approaches in modifying lead absorption in both acute and chronic situations. Lead distribution among blood components (RBC, plasma proteins and ultrafiltrate) will be studied and related to lead distribtuion to other tissues. Alteration in the distribution pattern of lead by other substances will be examined.